Ischemia-induced noradrenaline release in the isolated rat heart: influence of perfusion substrate and duration of ischemia.

To examine some of the characteristics of the local noradrenaline (NA) release in myocardial ischemia a study was made on Langendorff-perfused rat hearts, prelabelled with 3H-NA. The left coronary artery was ligated for 15, 30, 60 or 120 min, followed by 10 min of reperfusion. The coronary effluent was collected and analyzed for radioactivity to indicate release of 3H-NA. In some of the experiments the fraction of 3H-NA was determined. As substrate in the perfusion medium either glucose (11.1 mM) or sodium lactate (5.0 mM) was used. During the ischemic period there was a slight decrease in the outflow of radioactivity. However, reperfusion was associated with a rapid and marked outflow of radioactivity, including an increased fraction of 3H-NA, in the effluent. Compared to glucose as perfusion substrate, lactate caused a significantly higher (P less than 0.01) outflow of tritiated substances after 60 and 120 min of regional ischemia. With lactate there was an almost linear relationship between reperfusion efflux of 3H and duration of ischemia. With glucose, the reperfusion outflow increased less rapidly after a duration of ischemia longer than 15 min. It is concluded that the degree of local NA release in myocardial ischemia depends on both the duration of the ischemic period and the substrate used. Glucose attenuates the reperfusion outflow of NA, especially after longer periods of ischemia. The effect may be due to decreased myocardial cell damage with this substrate and/or a direct protection of the adrenergic nerve endings.